This is an open-label study to assess the pharmacokinetics, safety, efficacy and tolerability of SSP-004184AQ. The study consists of two phases: the pharmacokinetic phase, using a single 16 mg/kg dose of SSP-004184AQ; and the chronic dosing phase, during which patients will receive an additional 48 weeks of SSP-004184AQ dosing. Two age groups will be studied: 6-<12, and 12-<18 years old. The study is designed to initially assess the pharmacokinetics and safety of SSP-004184AQ in older children (adolescents, 12-<18 years old) and then if deemed safe, in younger children (6-<12 years old).

A Phase 2, Open Label, Multi-Center, Single-Dose Pharmacokinetics, and Multiple Dose Study of the Safety, Efficacy and Tolerability of SSP-004184 (SPD602) in a Pediatric Population With Transfusional Iron Overload

Single-dose Pharmacokinetics: The concentrations of FBS0701 will be measured in plasma from all patients using a validated assay method. Pharmacokinetic parameters will be tabulated and summarized. [ Time Frame: 8 days ] [ Designated as safety issue: Yes ]

Plasma levels, half-life of SSP-004184AQ and other pharmacokinetic parameters following a single capsule dose of SSP-004184AQ at 16 mg/kg with 7 days of follow-up.

Clinical assessments include incidence and severity of adverse events, physical examinations including vital signs, clinical laboratory values, and ECGs); clinical response to be evaluated based on changes in liver and cardiac iron concentration determined by MRI in patients able to be studied using this method; serum ferritin in all patients.

Parents willing and able to sign the approved informed consent for their children and subjects between the ages of 6 and <18 years willing and able to provide their assent (based on institutional guidelines).

Able to swallow whole capsules.

Age >6 and <18 years.

Transfusion-dependent subjects who have transfusional iron overload requiring chronic treatment with deferoxamine, deferasirox, or deferiprone. A transfusion dependent subject is defined in this study as one with a minimum transfusion history totaling more than 20 units of packed red blood cells OR a calculated iron load based on transfusion history of 200mg/kg AND a transfusion requirement of 7 or more transfusions per year; or, in subjects with sickle cell anemia, be iron overloaded but can be receiving transfusion exchange therapy in lieu of transfusions.

In the opinion of the Investigator (and in consultation with the subject's parents), the subject is able to discontinue all existing iron chelation therapies for a minimum period of 1-5 days prior first dose of SSP-004184AQ, for the initial pharmacokinetic period of 8 days (if applicable), and for up to 49 weeks if continuing into the chronic dosing phase.

cardiac MRI T2* >10ms (Note: Subjects not able to have an MRI will be considered iron overloaded on the basis of serum ferritin only.)

Serum ferritin >500ng/mL at Screening.

Mean of the previous 3 pre-transfusion hemoglobin concentrations greater than or equal to 7.5g/dL.

If appropriate, depending on age, female subjects of child-bearing potential need to use a medically acceptable method for birth control from screening until 30 days after the last dose of the study drug. Females of child-bearing potential must have a negative serum beta-HCG pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit. Females of child-bearing potential must agree to abstain from sexual activity that could result in pregnancy or agree to use acceptable methods of contraception.

Exclusion Criteria

As a result of medical review, physical examination (including height and weight) or Screening investigations, the Principal Investigator considers the subject unfit for the study.

Iron overload from causes other than transfusional hemosiderosis.

Severe cardiac dysfunction.

Non-elective hospitalization within the 30 days prior to Baseline testing.

Platelet count below 100,000/µL or absolute neutrophil count less than 1500/mm3 at Screening.

ALT >180 IU/L at Screening.

Use of any investigational agent within the 30 days prior to Baseline testing.

Pregnant or lactating females.

Cardiac left ventricular ejection fraction a) Below the locally determined normal range in the 12 months prior to screening by echocardiography or MRI or <50% at Baseline testing by MRI (echocardiograph is acceptable for LVEF if MRI information is not available).

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01363908